Regulation of lipid accumulation by new diabetes susceptible genes and the role of the epigenome
| Project Area | Molecular Basis and Disorders of Control of Apetite and Fat Accumulation |
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| Project/Area Number |
23126101
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | The University of Tokyo |
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Principal Investigator |
WAKI Hironori 東京大学, 医学部附属病院, 准教授 (00466765)
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| Co-Investigator(Kenkyū-buntansha) |
IWABU Masato 東京大学, 医学部附属病院, 特任助教 (30557236)
IWABU Miki 東京大学, 医学部附属病院, 特任助教 (70392529)
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| Co-Investigator(Renkei-kenkyūsha) |
YAMAUCHI Toshimasa 東京大学, 医学部附属病院, 准教授 (40372370)
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| Project Period (FY) |
2011-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥51,610,000 (Direct Cost: ¥39,700,000、Indirect Cost: ¥11,910,000)
Fiscal Year 2014: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2013: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2012: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
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| Keywords | 糖尿病 / 肥満 / 疾患感受性遺伝子 / 転写 / エピゲノム |
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| Outline of Final Research Achievements |
In this study, we found that expression of CDKAL1 - one of susceptible genes for type 2 diabetes and obesity identified in genome-wide association studies - is regulated during adipocyte differentiation, hypertrophy and adiposity. Functionally, CDKAL1 works as a factor that suppresses adipocyte differentiation and lipid accumulation. Mechanistically, we found that CDKAL1 stimulates the Wnt/β-catenin pathway, which suppresses adipocyte differentiation. We also mapped a promoter region responsible for the suppression of adiponectin gene expression in adipocyte hypertrophy. A transcription factor named Heb1 binds and regulates transcription. Expression level of Heb1 itlsef is regulated by various metabolic stress signals in adipocytes.
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Report
(5 results)
Research Products
(24 results)
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[Journal Article] Global mapping of cell type-specific open chromatin by FAIRE-seq reveals the regulatory role of the NFI family in adipocyte differentiation2011
Author(s)
Waki H, Nakamura M, Yamauchi T, Wakabayashi K, Yu J, Hirose-Yotsuya L, Take K, Sun W, Iwabu M, Okada-Iwabu M, Fujita T, Aoyama T, Tsutsumi S, Ueki K, Kodama T, Sakai J, Aburatani H, Kadowaki
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Journal Title
PLos Genetics
Volume: 7
Issue: 10
Pages: e1002311-e1002311
DOI
Related Report
Peer Reviewed
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[Presentation] Genome-wide Profiling of Brown Fat-Specific Open Regulatory Regions Identifies NFIA as a Transcriptional Regulator of Brown Fat Differentiation2014
Author(s)
Hironori Waki, Yuta Hiraike Jing Yu, Kana Miyake, Masahiro Nakamura, Ken Suzuki, Wei Sun, Megumi Tomioka, Yusuke Hirota, Tomohisa Aoyama, Masato Iwabu, Miki Okada-Iwabu, Kohjiro Ueki, Shuichi Tsutsumi, Hiroyuki Aburatani, Toshimasa Yamauchi and Takashi Kadowaki
Organizer
International Symposium for the Study of Obesity “Molecular Basis and Disorders of Control of Appetite and Fat Accumulation″
Place of Presentation
Miyazaki, Japan
Year and Date
2014-10-26
Related Report
Invited
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[Presentation] Genome-wide Profiling of Brown Fat-Specific Open Regulatory Regions Identifies NFIA as a Transcriptional Regulator of Brown Fat Muscle Cell Lineage Specification2014
Author(s)
Hironori Waki, Yuta Hiraike, Jing Yu, Kana Miyake, Masahiro Nakamura, Ken Suzuki, Kohjiro Ueki, Shuichi Tsutsumi, Hiroyuki Aburatani, Toshimasa Yamauchi, Takashi Kadowaki
Organizer
9th Metabolic Syndrome, Type 2 Diabetes and Atherosclerosis Congress
Place of Presentation
Kyoto, Japan
Year and Date
2014-09-13
Related Report
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[Presentation] CDK5 Regulatory Subunit-Associated Protein 1-Like 1 (Cdkal1) Negatively Regulates Adipocyte Differentiation through Activation of the Wnt Pathway2013
Author(s)
Kazumi Take, Hironori Waki, Toshimasa Yamauchi, Wei Sun, Jing Yu, Masato Iwabu, Miki Okada-Iwabu, Kohjiro Ueki, Takashi Kadowaki.
Organizer
American Diabetes Association 73nd Scientific Sessions
Place of Presentation
Chicago, IL, 米国
Related Report
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